The ability of many mammalian species to respond to in vivo challenges with complex antigens varies in a time dependent manner during embryonic and neonatal life. In utero and at birth immunologic competence is incomplete but the precise nature of the defect or defects is poorly understood. Studies are under way to elucidate the nature of immunologic unreactivity in neonatal mice utilizing a system of in vitro primary antibody response. It is of interest to determine how environmental exposure to antigens and the mammalian genome interact in controlling phenotypic expression of immune reactivity throughout development. Further studies may shed light on the time course of development of self tolerance.